Neurophysiological Assessments of Network Dysfunction in Alzheimer's Disease

阿尔茨海默病网络功能障碍的神经生理学评估

基本信息

批准号：
9916699
负责人：
Kamalini Gayathree Ranasinghe
金额：
$ 17.21万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916699
关键词：
Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease patient Amyloid beta-Protein Anatomy Animal Model Architecture Behavioral Biological Markers Biometry Brain Brain imaging California Clinical Clinical Research Clinical Trials Cognition Cognitive Cognitive aging Cognitive deficits Data Dementia Deposition Development Disease Disease Progression Environment Evaluation Frequencies Functional disorder Future Goals Grant Human Impaired cognition Impairment Investigation K-Series Research Career Programs Knowledge Link Magnetoencephalography Measures Medial Memory Mentors Molecular Nerve Degeneration Neurobiology Neurodegenerative Disorders Neurologist Neurons Neurosciences Pathologic Patients Pattern Physicians Play Positioning Attribute Positron-Emission Tomography Process Proteins Research Research Ethics Research Institute Research Personnel Research Project Grants Research Training Rest San Francisco Scientist Spatial Distribution Synapses Synaptic plasticity Syndrome Techniques Temporal Lobe Testing Therapeutic Intervention Tracer Training Translational Research Universities Work Writing abeta accumulation abeta deposition base brain behavior career career development cognitive ability design experience follow-up imaging study innovation insight knowledge base molecular imaging molecular marker multimodality network dysfunction neural circuit neural patterning neurobehavioral neurodegenerative dementia neuroimaging neuronal circuitry neurophysiology neuroregulation novel progressive neurodegeneration relating to nervous system spatiotemporal targeted treatment tau Proteins tau aggregation treatment strategy uptake

项目摘要

PROJECT SUMMARY This is an application for a K08 Mentored Clinical Scientist Research Career Development Award to promote the candidate's development as an independent researcher in clinical neuroscience, with a focus on understanding the neurophysiological abnormalities in Alzheimer's disease (AD), and eventually, in other dementia syndromes. Dr. Ranasinghe's long-term career goal is to develop a deep knowledge base on brain- behavior relationships associated with specific pathophysiological processes in neurodegenerative diseases. The current research project proposes a multimodal, longitudinal brain imaging study, integrating magnetoencephalographic imaging (MEGI) with positron emission tomography (PET), and with progressive trajectories of neurodegenerative processes, in AD patients. AIM-1 examines the distinct patterns of network synchronization deficits in patients with AD using MEGI, and their specific associations to PET-derived molecular markers of amyloid beta and tau. AIM-2 conducts longitudinal MEGI assessments of network deficits combined with cognitive and volumetric measures with annual follow-ups for two years. The results will uncover neurophysiological signatures of aberrant neuronal functions in AD, in humans, and will have important implications for translational research and clinical trials. This K08 will provide Dr. Ranasinghe with the support necessary to accomplish the following goals: (1) Training in application and analysis of multimodal neuroimaging techniques; (2) Clinical training in patient evaluations and longitudinal follow-up; (3) Gaining greater depth of knowledge in mechanisms of AD; (4) Training in advanced biostatistical analyses in clinical research; (5) Training in grant writing, career development, and research ethics. To achieve these goals, Dr. Ranasinghe has assembled a mentoring team including her primary mentor: Dr. Katherine Rankin (a neuropsychologist with expertise in neurodegenerative diseases); and two co-mentors: Drs. Gil Rabinovici (a behavioral neurologist with expertise in molecular imaging), and Srikantan Nagarajan (a neuroscientist with expertise in magnetoencephalography). The collaborators of Dr. Ranasingh'e project include Drs. Maria Luisa Gorno-Tempini (a behavioral neurologist with expertise in neuroimaging), Joel Kramer (a neuropsychologist with expertise in cognitive ageing), Lea Grinberg (a neuropathologist with expertise in neurobiology of AD), and Maria Glymour (a biostatistician). The candidate is a physician-scientist with a strong commitment to a career in neurodegenerative dementia research. The University of California San Francisco Memory and Aging Center is an ideal environment for the proposed training, being a top dementia research institute in the nation with access to world leading experts in clinical and translational research. The research and training experience described in this proposal will enable the candidate's goal of developing a strong independent research career in the field of neurophysiological assessments in neurodegenerative diseases.

项目摘要这是K08指导的临床科学家研究职业发展奖的申请，以促进候选人作为临床神经科学领域的独立研究人员的发展，重点是了解阿尔茨海默氏病（AD）的神经生理异常，最终在其他痴呆综合征。 Ranasinghe博士的长期职业目标是建立有关大脑的深刻知识基础 - 与神经退行性疾病中特定病理生理过程相关的行为关系。当前的研究项目提出了多模式的纵向大脑成像研究，整合带有正电子发射断层扫描（PET）的磁脑影像学成像（MEGI），并具有渐进性 AD患者中神经退行性过程的轨迹。 AIM-1检查网络的不同模式使用MEGI的AD患者的同步缺陷及其与PET衍生的特定关联淀粉样β和tau的分子标记。 AIM-2进行网络缺陷的纵向MEGI评估结合认知和体积措施，每年随访两年。结果将发现AD，人类中异常神经元功能的神经生理学特征，并将具有对翻译研究和临床试验的重要意义。该K08将为Ranasinghe博士提供实现以下目标所需的支持：（1）应用和分析多模式的培训神经影像技术；（2）患者评估和纵向随访的临床培训；（3）获得 AD机制的知识深度更大；（4）临床晚期生物统计分析的培训研究; （5）授予写作，职业发展和研究道德的培训。为了实现这些目标，博士 Ranasinghe组建了一个指导团队，包括她的主要导师：凯瑟琳·兰金（Katherine Rankin）博士（A 神经心理学家具有神经退行性疾病的专业知识）；和两个副官员：博士。吉尔·拉比诺维奇（a 具有分子成像专业知识的行为神经科医生）和Srikantan Nagarajan（具有神经科学家磁脑摄影的专业知识）。 Ranasingh'e项目的合作者包括Drs。玛丽亚·路易莎（Maria Luisa）戈尔诺·泰米（Gorno-Tempini）（神经影像学专业知识的行为神经科医生），乔尔·克雷默（Joel Kramer）（神经心理学家具有认知衰老的专业知识），Lea Grinberg（具有AD神经生物学专业知识的神经病理学家），并且 Maria Glymour（生物统计学家）。候选人是一名医师科学家，对职业有坚定的承诺在神经退行性痴呆研究中。加利福尼亚大学旧金山的记忆与老化中心是拟议培训的理想环境，是美国顶级痴呆研究所随着世界领先的临床和转化研究专家的机会。研究和培训本提案中描述的经验将使候选人的目标是建立强大的独立神经退行性疾病中神经生理评估领域的研究职业。